There were more than 1500 people in the two-storey Epitome Night Club on Chicago's South Side when someone released pepper spray or Mace into the air after 2am local time (7pm AEDT), Fire Commander Will Knight said.

"It appears a disturbance from within led to a mass chaos where people headed for the door. Most of the fatalities appear to have been crushed or had injuries due to suffocation," said police Officer Ozzie Rodriguez.

Cory Thomas, 33, of Chicago went to the club about 3am to pick up two friends. As he waited outside, he saw people inside the club start to back up against the glass front door.

"You could see a mound of people. People were stacking on top of each other, screaming and gagging, I guess from the pepper spray. The door got blocked because there were too many people stacked up against it," he said.

"I saw them taking out a pregnant woman," Mr Thomas said. "She was in bad shape. I saw at least 10 lifeless bodies."

Mr Knight said the total number of injuries was unclear because many of those with minor injuries were being taken to hospitals by family and friends.

The melee marks one of the nation's deadliest stampedes.

In December 1991, nine young people were crushed to death in a gymnasium stairwell while awaiting a celebrity basketball game in New York.

In December 1979, 11 people were killed in Cincinnati in a crush to get into a concert by The Who.